Pacing Output Configuration Selection for Cardiac Resynchronization Therapy Patients

ABSTRACT

Cardiac therapy systems include multiple electrodes respectively positionable at multiple left ventricular electrode sites. A pulse generator is coupled to the electrodes and configured to deliver a cardiac resynchronization therapy (CRT). A processor is configured to measure, for each left ventricular electrode site, a timing interval between first and second cardiac signal features associated with left ventricular depolarization. The timing interval is associated with a degree of responsiveness of each left ventricular electrode site to CRT. The processor is configured to determine a pacing output configuration that provides improved patient responsiveness to CRT based on the timing interval measurements and to select at least one left ventricular electrode site from the plurality of left ventricular electrode sites based on the timing interval measurements. The processor may be configured to monitor for a change in hemodynamic status of the patient based on a change in the timing interval.

RELATED APPLICATIONS

This application is a division of U.S. patent application Ser. No.11/654,938 filed on Jan. 18, 2007, to which Applicant claims priorityunder 35 U.S.C. §120, and which is incorporated herein by reference.

FIELD OF THE DISCLOSURE

The present invention relates generally to cardiac pacing devices andtherapies, and more specifically, to systems and methods for selecting apacing output configuration that improves a patient's responsiveness tocardiac resynchronization therapy.

BACKGROUND

When functioning normally, the heart produces rhythmic contractions andis capable of pumping blood throughout the body. The heart hasspecialized conduction pathways in both the atria and the ventriclesthat enable the rapid conduction of excitation impulses (i.e.depolarizations) from the SA node throughout the myocardium. Thesespecialized conduction pathways conduct the depolarizations from the SAnode to the atrial myocardium, to the atrio-ventricular node, and to theventricular myocardium to produce a coordinated contraction of bothatria and both ventricles.

The conduction pathways synchronize the contractions of the musclefibers of each chamber as well as the contraction of each atrium orventricle with the opposite atrium or ventricle. Without thesynchronization afforded by the normally functioning specializedconduction pathways, the heart's pumping efficiency is greatlydiminished. Patients who exhibit pathology of these conduction pathwayscan suffer compromised cardiac output.

Normally, the muscular walls of each chamber of the heart contractsynchronously in a precise sequence to efficiently circulate bloodthrough the heart. In particular, both the right and left atriumscontract (e.g., atrial contractions) and relax synchronously. Shortlyafter the atrial contractions, both the right and left ventriclescontract (e.g., ventricular contractions) and relax synchronously.Several disorders or arrhythmias of the heart can prevent the heart fromoperating normally, such as, blockage of the conduction system, heartdisease (e.g., coronary artery disease), abnormal heart valve function,or heart failure.

Blockage in the conduction system can cause a slight or severe delay inthe electrical impulses propagating through the atrioventricular node,causing inadequate ventricular contractions and filling. In situationswhere the blockage is in the ventricles (e.g., the right and left bundlebranches), the right and/or left ventricles can only be excited throughslow muscle tissue conduction. As a result, the muscular walls of theaffected ventricle do not contract synchronously (e.g., asynchronouscontraction), thereby, reducing the overall effectiveness of the heartto pump oxygen-rich blood throughout the body.

Cardiac rhythm management devices have been developed that providepacing stimulation to one or more heart chambers in an attempt toimprove the rhythm and coordination of atrial and/or ventricularcontractions. Cardiac rhythm management devices typically includecircuitry to sense signals from the heart and a pulse generator forproviding electrical stimulation to the heart. Leads extending into thepatient's heart chamber and/or into veins of the heart are coupled toelectrodes that sense the heart's electrical signals and deliverelectrical stimulation to the heart in accordance with various therapiesfor treating cardiac arrhythmias.

Pacemakers are cardiac rhythm management devices that deliver a seriesof low energy pace pulses timed to assist the heart in producing acontractile rhythm that maintains cardiac pumping efficiency. Pacepulses may be intermittent or continuous, depending on the needs of thepatient. There exist a number of categories of pacemaker devices, withvarious modes for sensing and pacing one or more heart chambers.

Pacing therapy has been used in the treatment of heart failure (HF).Heart failure causes diminished pumping power of the heart, resulting inthe inability to deliver enough blood to meet the demands of peripheraltissues. Heart failure may affect the left heart, right heart or bothsides of the heart, and may cause weakness, loss of breath, and build upof fluids in the lungs and other body tissues. For example, HF may occurwhen deterioration of the muscles of the heart produce an enlargement ofthe heart and/or reduced contractility. The reduced contractilitydecreases the cardiac output of blood and may result in an increasedheart rate. In some cases, HF is caused by unsynchronized contractionsof the left and right heart chambers, denoted atrial or ventriculardysynchrony. Particularly when the left or right ventricles areaffected, the unsynchronized contractions can significantly decrease thepumping efficiency of the heart.

Pacing therapy to promote synchronization of heart chamber contractionsto improve cardiac function is generally referred to as cardiacresynchronization therapy (CRT). Some cardiac pacemakers are capable ofdelivering CRT by pacing multiple heart chambers. Pacing pulses aredelivered to the heart chambers in a sequence that causes the heartchambers to contract in synchrony, increasing the pumping power of theheart and delivering more blood to the peripheral tissues of the body.In the case of dysynchrony of right and left ventricular contractions, abiventricular pacing therapy may pace one or both ventricles. Bi-atrialpacing or pacing of all four heart chambers may alternatively be used.

SUMMARY

The present invention is directed to systems and methods for selecting apacing output configuration that improves a patient's responsiveness tocardiac resynchronization therapy (CRT). Embodiments of the presentinvention are directed to cardiac therapy systems that include multipleelectrodes respectively positionable at multiple locations within atleast a left ventricle for sensing cardiac electrical signals from aplurality of left ventricular electrode sites. A pulse generator iscoupled to the multiple electrodes and configured to deliver at least aCRT.

A processor is coupled to the multiple electrodes and the pulsegenerator. The processor is configured to measure, for each leftventricular electrode site, a timing interval between first and secondcardiac signal features associated with left ventricular depolarization.The timing interval is preferably associated with a degree ofresponsiveness of each left ventricular electrode site to CRT. Theprocessor is configured to determine a pacing output configuration thatprovides improved patient responsiveness to CRT based on the timinginterval measurements and to select at least one left ventricularelectrode site from the plurality of left ventricular electrode sitesbased on the timing interval measurements.

In accordance with other embodiments, cardiac therapy systems of thepresent invention may be configured to include multiple electrodesrespectively positionable at multiple locations within at least a leftventricle for sensing cardiac electrical signals from at least one leftventricular electrode site, and a pulse generator coupled to themultiple electrodes and configured to deliver at least a CRT. Aprocessor is coupled to the multiple electrodes and the pulse generator.The processor is configured to detect a change in a timing intervalbetween first and second cardiac signal features associated withventricular depolarization, the timing interval associated with a degreeof responsiveness of the at least one left ventricular electrode site toCRT. The processor is configured to monitor for a change in hemodynamicstatus of the patient based on the detected timing interval change.

According to further embodiments, methods of the present invention maybe implemented that involve sensing of cardiac electrical signals from aplurality of left ventricular electrode sites, and measuring, for eachleft ventricular electrode site, a timing interval between first andsecond cardiac signal features associated with left ventriculardepolarization. The timing interval is preferably associated with adegree of responsiveness of each left ventricular electrode site to CRT.A pacing output configuration is determined that provides improvedpatient responsiveness to CRT based on the timing interval measurements.Determining the pacing output configuration may include selecting atleast one left ventricular electrode site from the plurality of leftventricular electrode sites based on the timing interval measurements.

In accordance with other embodiments, methods of the present inventionmay be implemented that involve sensing, from within a patient, one ormore cardiac electrical signals, including a cardiac electrical signalfrom at least one left ventricular electrode site. A change in a timinginterval between first and second cardiac electrical signal featuresassociated with ventricular depolarization may be detected, the timinginterval associated with a degree of responsiveness of the at least oneleft ventricular electrode site to a CRT. Methods may further involvemonitoring for a change in hemodynamic status of the patient based onthe detected timing interval change.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a patient-implantable therapy device that may beconfigured to implement a pacing output configuration selectionmethodology in accordance with embodiments of the invention;

FIG. 2 is a block diagram of circuitry used to select a pacing outputconfiguration in accordance with embodiments of the invention;

FIG. 3 is a flow diagram illustrating a process for selecting a pacingoutput configuration in accordance with embodiments of the invention;

FIG. 4 is a flow diagram illustrating another process for determining apacing output configuration in accordance with embodiments of theinvention;

FIG. 5 is a flow diagram illustrating a process for monitoring and/ortracking changes in a patient's hemodynamic status in accordance withembodiments of the invention;

FIG. 6 is a flow diagram illustrating various processes for determininga pacing output configuration and monitoring/tracking changes in apatient's hemodynamic status in accordance with embodiments of theinvention;

FIG. 7 illustrates is a series of cardiac signal waveforms associatedwith ventricular depolarization, which includes features useful fordetermining timing intervals for implementing a pacing outputconfiguration selection methodology in accordance with embodiments ofthe invention; and

FIG. 8 illustrates cardiac signal waveforms taken from various leftventricular electrode sites and time intervals associated with each sitein accordance with embodiments of the invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings, which form a part hereof, and inwhich is shown by way of illustration, various embodiments in which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

Systems, devices or methods according to the present invention mayinclude one or more of the features, structures, methods, orcombinations thereof described hereinbelow. For example, a device orsystem may be implemented to include one or more of the advantageousfeatures and/or processes described below. It is intended that suchdevice or system need not include all of the features described herein,but may be implemented to include selected features that provide foruseful structures and/or functionality. Such a device or system may beimplemented to provide a variety of therapeutic or diagnostic functions.

A cardiac therapy device implemented in accordance with the presentinvention may deliver electrical stimulation pulses to one or moreelectrodes disposed within a heart chamber and/or otherwise electricallycoupled to the myocardium to initiate contractions of the chamber.Embodiments of the invention are directed to systems and methods forselecting a pacing output configuration that improves a patient'sresponsiveness to cardiac resynchronization therapy. Embodiments of theinvention are directed to systems and methods for measuring, for each ofa number of different electrode sites, a timing interval betweenspecified cardiac signal features associated with left ventriculardepolarization, where the timing interval is reflective of a degree ofresponsiveness of each electrode site to CRT. Based on the timingintervals associated with the electrode sites, a pacing outputconfiguration is determined, which preferably includes a least a pacingsite selected from the various electrode sites or a pacing vectorassociated with the selected pacing site. The pacing outputconfiguration may also include selection of one or more pacingparameters, such as AV delay, based on pacing site selection.

Electrode site selection is preferably based on timing intervalmeasurements associated with ventricular depolarization. These timinginterval measurements may be used to identify and/or select electrodesites(s) that provide for improved responsiveness to cardiacresynchronization therapy. Changes in such measured timing intervals maybe monitored to evaluate changes in a patient's hemodynamic status,generate warnings in response to measurements that change beyond athreshold, and/or to modify electrode site selection and/or a pacingparameter (e.g., AV delay) to improve patient responsiveness to CRT andthe patient's hemodynamic status.

According to various embodiments, electrode sites may be evaluated toidentify those that will respond to CRT (referred to herein as“responder sites”), and such identified responder sites may be furtherevaluated to determine their relative degree of responsiveness to CRT.Responder sites may be characterized by late activation ofdepolarization and/or prolonged depolarization. Electrode sitecharacterization may be implemented through analysis of a timinginterval (e.g., Q1-LV or Q-LV) defined between a first deflection (e.g.,Q1 or Q) and a maximum deflection (e.g., LV) of a ventriculardepolarization for a given electrode site. The Q1-LV timing intervalrefers to a timing interval defined between the start of a QRSdeflection of the LV electrogram and the peak of the QRS deflection ofthe LV electrogram. The Q-LV timing interval refers to a timing intervaldefined between the start of a QRS deflection of a surface ECG and thepeak of the QRS deflection of the LV electrogram.

A relationship exists between the intrinsic depolarization interval(e.g., Q1-LV or Q-LV) and the increase in peak rate of increase of leftventricle pressure (LV dp/dt) due to CRT, both of which are associatedwith greater cardiac output. Intervals associated with various cardiacelectrode sites can be compared, preferably by an implantable therapydevice or a patient-external processor, to determine the most effectiveand/or efficient pacing output configuration. Such comparisons may berepeated over time to determine if changes to the pacing outputconfiguration can be made that will improve patient responsiveness toCRT. Changes to the pacing output configuration may include a change toone or more of the pacing electrode site(s), pacing vector(s), andpacing parameter(s), such as AV delay.

The patient's Q1-LV or Q-LV timing interval may be monitored andtracked, such as by the therapy device and/or by a programmer oradvanced patient management system. Changes in the patient's Q1-LV orQ-LV timing interval relative to a threshold may be used to detect anadverse change in the patient's hemodynamic status. Changes in thepatient's Q1-LV or Q-LV timing interval may also be monitored to trackthe progression or regression of a patient's heart failure status.

If the patient's Q1-LV or Q-LV timing interval falls below a threshold,a clinician alert may be generated. A change in this timing intervalrelative to a threshold may trigger a re-optimization procedure, wherebyavailable electrode sites/vectors are re-evaluated to determine if analternative electrode site having a greater intrinsic depolarizationtiming interval than that associated with a current pacing outputconfiguration is available. If so, the therapy device may be programmedto automatically select a pacing output configuration that includes thealternative electrode site. A pacing parameter, such as AV delay, mayalso be adjusted in response to selection of the alternative electrodesite. Alternatively, a physician may be notified that a change in pacingoutput configuration is needed or desired. The physician may then modifythe pacing output configuration accordingly, such as by use of aprogrammer of advanced patient management system.

Turning now to FIG. 1, there is shown a therapy device 100 thatrepresents one of several possible embodiments of a patient-implantabledevice that may be used in conjunction with pacing output configurationdeterminations made in accordance with the present invention. Thetherapy device 100 includes cardiac rhythm management (CRM) circuitryenclosed within an implantable housing 101. The CRM circuitry iselectrically coupled to an intracardiac lead system 110.

Portions of the intracardiac lead system 110 are shown inserted into thepatient's heart. The lead system 110 includes cardiac pace/senseelectrodes 151-156 positioned in, on, or about one or more heartchambers for sensing electrical signals from the patient's heart and/ordelivering pacing pulses to the heart. The intracardiac sense/paceelectrodes 151-156, such as those illustrated in FIG. 1, may be used tosense and/or pace one or more chambers of the heart, including the leftventricle, the right ventricle, the left atrium and/or the right atrium.The lead system 110 is shown to include one or more defibrillationelectrodes 141, 142 for delivering defibrillation/cardioversion shocksto the heart.

The left ventricular lead 105 incorporates multiple electrodes 154 a-154d positioned at various locations within, on or about the leftventricle. Stimulating the ventricle at multiple locations or at asingle selected location may provide for increased cardiac output in apatients suffering from HF. In accordance with various embodimentsdescribed herein, one or more of the electrodes 154 a-154 d are selectedfor pacing the left ventricle. In other embodiments, leads havingmultiple pacing electrodes positioned at multiple locations within achamber, such as the one illustrated by the left ventricular lead 105 ofFIG. 1, may be implanted within any or all of the heart chambers. One ormore electrodes positioned within one or more chambers may be selectedbased on timing interval measurements as described herein. Electricalstimulation pulses may be delivered to the chambers via the selectedelectrodes according to a timing sequence and output configuration thatenhances cardiac function.

Portions of the housing 101 of the implantable device 100 may optionallyserve as one or multiple can or indifferent electrodes. The housing 101is illustrated as incorporating a header 189 that may be configured tofacilitate removable attachment between one or more leads and thehousing 101. The housing 101 of the therapy device 100 may include oneor more can electrodes 181 b, 181 c. The header 189 of the therapydevice 100 may include one or more indifferent electrodes 181 a. Thehousing 101 and/or header 189 may include any number of electrodespositioned anywhere in or on the housing 101 and/or header 189.

The cardiac electrodes and/or other sensors disposed within or on thehousing 101 or lead system 110 of the therapy device 100 may producesignals used for detection and/or measurement of various physiologicalparameters, such as transthoracic impedance, respiration rate, minuteventilation, heart rate, cardiac dysynchrony, activity, posture, bloodchemistry, O2 saturation, heart sounds, wall stress, wall strain,hypertrophy, inter-electrode impedance, electrical delays (PR interval,AV interval, QRS width, etc.), activity, cardiac chamber pressure (e.g.,left ventricular pressure), cardiac output, temperature, heart ratevariability, depolarization amplitudes, depolarization timing, and/orother physiological parameters.

For example, in some configurations, the implantable device 100 mayincorporate one or more transthoracic impedance sensors that may be usedto acquire the patient's respiratory waveform, and/or to acquire otherrespiratory-related information. The transthoracic impedance sensor mayinclude, for example, one or more intracardiac electrodes 141, 142,151-156 positioned in one or more chambers of the heart. Theintracardiac electrodes 141, 142, 151-156 may be coupled to impedancedrive/sense circuitry positioned within the housing 101 of the therapydevice 100. Information from the transthoracic impedance sensor may beused to adapt the rate of pacing to correspond to the patient's activityor metabolic need.

Communications circuitry is disposed within the housing 101 forfacilitating communication between the CRM circuitry and apatient-external device, such as an external programmer or advancedpatient management (APM) system. The communications circuitry may alsofacilitate unidirectional or bidirectional communication with one ormore implanted, external, cutaneous, or subcutaneous physiologic ornon-physiologic sensors, patient-input devices and/or informationsystems.

In certain embodiments, the therapy device 100 may include circuitry fordetecting and treating cardiac tachyarrhythmia via defibrillationtherapy and/or anti-tachyarrhythmia pacing (ATP). Configurationsproviding defibrillation capability may make use of defibrillation coils141, 142 for delivering high energy shocks to the heart to terminate ormitigate tachyarrhythmia. It is understood that defibrillation coils141, 142 are employed in therapy devices 100 that provide for bothpacing and cardioversion/defibrillation functionality.

In some embodiments, the implantable therapy device 100 may includecircuitry for selection of pacing electrode(s), electrode sites,timing/delay sequences and/or pacing output configuration to be appliedvia one or more electrodes. In other embodiments, the therapy device 100may diagnose a change in a patient's hemodynamic status based on timinginterval measurements derived from signals sensed from one or moreelectrodes, such as electrodes 154A-D, or from signals derived from oneor more hemodynamic sensors, such as a pressure sensor.

In other embodiments, the implantable therapy device 100 may transfersensed or derived information relevant to pacing output configuration ordiagnosis to a patient-external device. Following download of theimplantably sensed or derived information, selection of the pacingoutput configuration or a diagnosis of hemodynamic status may be made bythe patient-external device or may be made by a clinician usinginformation provided via the patient-external device.

Pacing output configuration involves selection of the site or sites ofpacing within a heart chamber and/or temporal sequence of the pacingpulses delivered to the multiple sites, and may also optionally involveselection of particular pulse characteristics (e.g., amplitude,duration, anodal/cathodal polarity, AV interval, and waveshape) used forthe pacing pulses. Selection of the pacing output configuration isparticularly desirable for optimal application of cardiacresynchronization therapy.

Heart failure, long term pacing, ischemia, myocardial infarction and/orother factors can produce non-uniformities in the electrical, mechanicalor electromechanical properties of the myocardium. Thesenon-uniformities can cause a heart chamber to contract in anuncoordinated manner resulting in inefficient pumping action. Thelocation of the pacing site or sites and/or other properties of thepacing output configuration affects the spread of the depolarizationexcitation which in part determines the manner in which the chambercontracts. In a pacemaker equipped with multiple pacing electrodesrespectively disposed at multiple pacing sites within a heart chamber,the ability to select between one or more electrodes, temporal sequence,and/or pulse waveform characteristics for delivery of pacing can be usedenhance the contractile function of the heart chamber.

Multi-site pacemakers, such as illustrated herein, are capable ofdelivering pacing pulses to multiple sites of the atria and/orventricles during a cardiac cycle. Certain patients may benefit fromactivation of parts of a heart chamber, such as a ventricle, atdifferent times in order to distribute the pumping load and/ordepolarization sequence to different areas of the ventricle. Amulti-site pacemaker has the capability of switching the output ofpacing pulses between selected electrodes or groups of electrodes withina heart chamber during different cardiac cycles. For example, the pacingpulses may be delivered to the heart chamber at specified locations andat specified times during the cardiac cycle to enhance the synchrony ofthe contraction. Amplitude, pulse duration, anodal/cathodal polarityand/or waveshape of the pacing pulses may also be altered to enhancepumping function.

Various abnormalities of the heart can change the pumping efficiency ofthe heart. Various arrhythmias include an abnormally fast heart rate(e.g., tachycardia), an abnormally slow heart rate (e.g., bradycardia),or a normal rate but where the depolarization is abnormally propagated(e.g., ectopic, or conduction system defect). The existence of anarrhythmia typically indicates that the heart's rhythm initiation and/orconduction system is functioning abnormally. Cardiac resynchronizationtherapy can be used, among other applications, to treat abnormalelectrical conduction.

In particular, CRT can be used to deliver electrical stimulation toportions of the heart to resynchronize the heart's activation, thereby,improving the efficiency of atrial and ventricular contractionsnecessary to circulate blood throughout the body. The amount of benefitderived from CRT, however, typically varies depending upon the severityof the abnormality of the heart's conduction system. Therefore, prior tocardiac electrode placement or cardiac electrode output configuration,it is preferable to evaluate whether the heart's conduction system isnormal or abnormal and whether stimulation will improve cardiac output.

Not all possible cardiac electrode sites in the ventricles are ideal foreffective cardiac pacing. For example, various cardiac electrode sitesof a particular patient's left ventricle may not significantly improveoverall cardiac output when paced. Other cardiac electrode sites maysignificantly improve overall cardiac output when paced. Cardiacelectrode sites that sufficiently improve the overall cardiac outputwhen paced are called responder sites. Cardiac electrode sites that donot sufficiently improve the overall cardiac output when paced arecalled non-responder sites.

In various embodiments of the present invention, a pacing outputconfiguration for delivering CRT by an implantable cardiac therapydevice is selected and/or modified based on timing interval measurementsderived from a number of such responder sites, initially during implantand thereafter during post-implant CRT delivery. Monitoring such timinginterval measurements over time allows for tracking of changes inpatient responsiveness to CRT, changes in patient hemodynamic status,and, if needed, re-optimization of selected electrode/responder sites.

Responder sites can be characterized by late activation ofdepolarization and/or prolonged depolarization. These can be assessedthrough analysis of the interval (Q1-LV or Q-LV) from the firstdeflection (Q1 or Q) to the maximum deflection (LV) at the stimulationsite of the ventricular depolarization, as is discussed in greaterdetail in commonly owned U.S. Pat. Nos. 5,235,976, 6,993,389, and7,142,922 which are hereby incorporated herein by reference.

As was discussed previously, a relationship exists between the intrinsicdepolarization interval (e.g., Q1-LV or Q-LV) and the increase in peakrate of increase of left ventricle pressure (LV dp/dt) due to CRT, bothof which are associated with greater cardiac output. Intervalsassociated with various cardiac electrode sites can be compared,preferably by an implantable therapy device or a patient-externalprocessor, to determine the most effective and/or efficient pacingoutput configuration. Such comparisons may be repeated over time todetermine if changes to the pacing output configuration can be made thatwill improve patient responsiveness to CRT. Changes to the pacing outputconfiguration may include a change to one or more of the pacingelectrode site(s), pacing vector(s), and pacing parameter(s), such as AVdelay.

Identification and prioritization of stimulation sites that may have apositive response to CRT can be performed using the intervals describedabove, where at least the maximum deflection point (LV) is preferablymeasured from an intracardiac electrogram. For example, if the timinginterval (Q1-LV or Q-LV) for a particular electrode site is greater thanan equivalent timing interval for other electrode sites, then theparticular electrode site may be considered a higher priority whenconsidering whether, and in what configuration, to deliver CRT to theelectrode sites.

Embodiments of the invention are directed to methods for configuring thepacing output configuration of a cardiac therapy device by evaluating aninterval of a sensed signal for a particular cardiac electrode site, theinterval defined between a first deflection to a maximum deflection ofdepolarization of a ventricle. The duration of this interval, which istypically compared to a threshold, indicates whether or not the cardiacelectrode site will respond to CRT. A typical threshold associated withthe Q1-LV timing interval is about 100 ms. A typical thresholdassociated with the Q-LV timing interval is about 80 ms. Methods of thepresent invention may also involve comparing the timing interval toother sensed intervals for various cardiac electrode sites andconfiguring the cardiac pacing output configuration, such as electrodesite/vector selection and pacing parameter (e.g., AV delay) adjustment,based on the comparison.

FIG. 2 is a block diagram of circuitry used for establishing andadjusting the pacing output configuration of a cardiac therapy device inaccordance with embodiments of the present invention. Multiple cardiacelectrodes 245 are disposed at multiple locations within or on a heartchamber, such as in a manner previously discussed. Intrinsic cardiacsignals, such as signals associated with ventricular depolarization, maybe collected by cardiac electrodes 245 and then received by the cardiacsignal sensing circuitry 240.

One or more sensors 210 are configured to sense physiological factorsindicative of a patient's hemodynamic status. The sensors 210 may beimplantable, cutaneous or other type of sensor. For example, one or moresensors 210 may be disposed within or on the housing or lead system ofthe therapy device and produce signals used for detection and/ormeasurement of various physiological parameters indicative of apatient's hemodynamic status. Such sensors 210 and/or cardiac electrodes245 may be configured, for example, to sense transthoracic impedance,respiration rate, minute ventilation, heart rate, cardiac dysynchrony,activity, posture, blood chemistry, O2 saturation, heart sounds, wallstress, wall strain, hypertrophy, inter-electrode impedance, electricaldelays (PR interval, AV interval, QRS width, etc.), activity, cardiacchamber pressure, cardiac output, temperature, heart rate variability,depolarization amplitudes, depolarization timing, and/or otherphysiological parameters.

According to one approach, a detected change in hemodynamic status ofthe patient may trigger a check to determine if a change in the pacingoutput configuration would be beneficial. In various implementations,one or more of the hemodynamic status sensors 210 used to triggerre-evaluation of the pacing output configuration may be selectable bythe therapy device or by a clinician, such as by way of an APM systeminterface. The hemodynamic status sensor(s) 210 may also be used tomonitor changes in the patient's hemodynamic status to verify thatchanges to the pacing output configuration improve the patient'sresponsiveness to CRT.

The therapy control processor 230, for example, may be configured toassess CRT responsiveness for each of a number of electrode sites. Forexample, the therapy control processor 230, in conjunction with thecardiac electrodes 245, may assess a parameter associated with a degreeof responsiveness of a left ventricular electrode site to cardiacresynchronization. Such parameters may include depolarizationcharacteristics such as depolarization delays (e.g., Q1-LV or Q-LVinterval), atrioventricular timing intervals, depolarization amplitude,depolarization-repolarization intervals, depolarization thresholds,and/or other depolarization characteristics. The therapy controlprocessor 230 may be configured to identify features of a sensed signalcorresponding to an atrial and/or ventriculardepolarization/repolarization. Such features may include the start ofventricular depolarization, a peak initial deflection corresponding toventricular depolarization, and a maximum deflection associated withventricular depolarization, among other features.

In one embodiment, depolarization timing intervals may be measured ateach electrode site during an intrinsic systolic contraction. Adistribution of the depolarization timing intervals can be determined bymeasuring the time interval between the start of ventriculardepolarization and a maximum signal deflection associated withventricular depolarization detected via cardiac electrograms sensed ateach of the cardiac electrodes during the contraction.

In accordance with some embodiments, cardiac sensing circuitry 240 mayinclude individual sense amplifiers and peak detectors for eachelectrode in the ventricle. In other embodiments, a bipolar sensingtechnique may be used to reduce the number of sense amplifiers and/orother signal processing circuitry required to detect the depolarizationdelay distribution. Measurement of the distribution of depolarizationtiming intervals in a heart chamber may be accomplished using thetechniques described in commonly owned U.S. Pat. Nos. 7,239,913 or7,697,977, which are incorporated herein by reference.

After measurement of the parameter associated with a degree ofresponsiveness of an electrode site to CRT, pacing output controlcircuitry 235 selects an appropriate pacing output configuration.According to one aspect, the pacing output control circuitry 235 mayselect an electrode corresponding to a pacing site having a longestdepolarization timing interval or may select a number of electrodes forpacing in a pattern or sequence based on their respective depolarizationtiming intervals. In some configurations, the electrode associated withthe longest depolarization timing interval may be paced first, theelectrode associated with the second longest interval may be paced next,and so forth.

As described above, one way of selecting a pacing site forresynchronization therapy is to measure the depolarization delays of anumber of potential pacing sites. One or more sites that aredemonstrated to be excited later in the contraction sequence may then beselected as pacing sites. Pacing the latest activated site or pacingmultiple sites in a sequence corresponding to their respective timingintervals may provide for a more coordinated contraction profile.

The embodiment illustrated in FIG. 2 also includes a switch matrix 260.The switch matrix 260 can arrange the pacing pulses delivered throughthe various electrodes 245 as directed by the pacing output controlcircuitry 235. The switch matrix 260 can also receive pacing pulses frompulse generator 270 and route the pacing pulses to the appropriatecardiac electrodes 245 as directed by the pacing output controlcircuitry 235.

Circuitry for assessing CRT responsiveness of a number of electrodesites and determining an appropriate pacing output configuration may beprovided in the therapy device 201. In one embodiment, thecomponents/processes included within the dashed line 201 of FIG. 2 maybe provided by an implantable therapy device such as that illustrated inFIG. 1. Such a device may include a power supply (not shown) and memory245 for storing program instructions and/or data. In variousconfigurations, the memory 245 may be used to store informationassociated with CRT responsiveness assessment, change in hemodynamiccondition, and/or present and past pacing output configurations. Theinformation stored in the memory 245 may be used to create a lookuptable for future reference that may be used to facilitate selection of abeneficial pacing output configuration. In addition, the storedinformation may be used to provide a log of events for display oranalysis at a later time. The therapy device 201 also includescommunications circuitry 215 for communicating with a patient-externaldevice 205, such as a programmer or advanced patient management system.

In some configurations, the implantable device may provide some of thefunctionality for selection of pacing output configuration, and apatient-external device may provide some of the functionality. Forexample, in one embodiment, the patient-external device communicateswith the implantable device over a telemetry link and receives eitherraw data, markers corresponding to particular sensed events, and/ormeasurements of timing intervals or other signal characteristics asdetermined by the implantable device. The external device may thengenerate CRT responsiveness data and compute optimal settings for thepacing output configuration which are either transmitted to theimplantable device for immediate reprogramming, or presented to aclinician operating the external device as a recommendation.Alternatively, the external device may present the raw data, markersand/or measurements to the clinician who may then program theimplantable device in accordance with an algorithm.

FIG. 3 is a flow graph illustrating an approach for selecting the pacingoutput configuration of a therapy device to improve a patient'sresponsiveness to CRT in accordance with one embodiment of the presentinvention. In this illustrative example, optimization of the pacingoutput configuration is based on a numerical distribution of CRTresponsiveness of left ventricular electrode sites. According to oneapproach, a parameter associated with a degree of responsiveness of aleft ventricular electrode site to CRT is measured 310 at a number ofleft ventricular electrode sites. The parameter can include varioustiming intervals of left ventricular depolarization as discussed herein.

Once parameters are measured for the left ventricular electrode sites, anumerical distribution of CRT responsiveness for the left ventricularelectrode sites is determined 320, the distribution characterizingrelative degrees of CRT responsiveness. The distribution may beorganized in various ways, depending on the nature of the parameter andthe measurement. In an embodiment in which the parameter is a timinginterval associated with ventricular depolarization, the distributionmay be organized according to the various lengths of the timing intervalmeasured. The numerical distribution may then be used to select 330 apacing output configuration for CRT. Pacing sites with greaterresponsiveness to CRT, according to the distribution, may be more likelyto receive pacing stimulation than pacing sites with relatively lessresponsiveness to CRT.

FIG. 4 is a flow graph illustrating an approach for selecting a pacingoutput configuration of a therapy device to improve a patient'sresponsiveness to CRT in accordance with another embodiment of thepresent invention. In this illustrative example, optimization of thepacing output configuration is based on a comparison of timing intervalsassociated with ventricular depolarization at a number of leftventricular electrode sites. According to one approach, cardiacelectrode signals for a number of left ventricular electrode sites aresensed 410. After the left ventricular cardiac electrode signals aresensed, each from a left ventricular electrode site, a timing intervalbetween first and second cardiac signal features associated withventricular depolarization is measured 420 for each left ventricularelectrode site, where the timing interval is associated with a degree ofresponsiveness of the left ventricular electrode site to CRT.

For example, a timing interval of a sensed left ventriculardepolarization may be measured. The timing interval may be measured bycalculating the time between when a first feature of an electrogram(EGM) or electrocardiogram (ECG) signal associated with left ventriculardepolarization is sensed and a second feature of an EGM or ECG signalassociated with left ventricular depolarization is sensed. The firstfeature may be the peak of a first deflection of ventriculardepolarization and the second feature may be the maximum deflection ofventricular depolarization. By way of example, the first feature may bethe first deflection of left ventricular depolarization represented byQ1 or Q, and the second feature may be the maximum deflection ofventricular depolarization, represented by LV. The process of measuringtime intervals according to block 420 is repeated for each of the leftventricular electrode sites. As discussed herein, the timing intervalfor each electrode site may be indicative of a degree of responsivenessof the electrode site to CRT.

After timing intervals are measured for the left ventricular electrodesites, at least one left ventricular electrode site timing interval iscompared 430 to a timing interval of at least one other left ventricularelectrode site. Preferably, the measured timing intervals are comparedto one another so as to determine the timing interval of greatestduration. The comparison may be done in various ways, depending on thenature of the timing interval and the measurement.

The comparison 430 may then be used to determine 440 a pacing outputconfiguration for CRT. Pacing sites with greater responsiveness to CRT,according to the comparison, may be more likely to receive pacingstimulation than pacing sites with relatively less responsiveness toCRT. If the comparison is made according to the length of a timeinterval, then the electrode site with the longest time interval mayhave priority in the pacing output configuration and, as such, may bemore likely to receive pacing stimulation or receive pacing stimulationbefore other electrode sites.

FIG. 5 is a flow graph illustrating a process for monitoring a patient'shemodynamic status in accordance with another embodiment of the presentinvention. In this illustrative example, changes in a patient'shemodynamic status are detected based on changes in timing intervalsassociated with ventricular depolarization at a number of leftventricular electrode sites. According to one approach, cardiacelectrode signals for a number of left ventricular electrode sites aresensed 710. After the left ventricular cardiac electrode signals aresensed, each from a left ventricular electrode site, a timing intervalbetween first and second cardiac signal features associated withventricular depolarization is measured for each left ventricularelectrode site, where the timing interval is associated with a degree ofresponsiveness of the left ventricular electrode site to CRT. Changes inthe timing interval for each left ventricular electrode site aredetected 720, such as by comparing changes in each timing intervalrelative to a threshold as previously discussed or by detecting astatistically significant change in the timing interval (e.g., changeof >20 ms; >20%; >3 sigma standard deviation). Changes in the patient'shemodynamic status may monitored and tracked 730 based on the detectedtiming interval changes.

FIG. 6 is a flow graph illustrating a process for optimizing electrodesite selection and monitoring a patient's hemodynamic status inaccordance with an embodiment of the present invention. In thisillustrative example, cardiac electrode signals for a number of leftventricular electrode sites are sensed 810. After the left ventricularcardiac electrode signals are sensed, each from a left ventricularelectrode site, a timing interval between first and second cardiacsignal features associated with ventricular depolarization is measuredfor each left ventricular electrode site, where the timing interval isassociated with a degree of responsiveness of the left ventricularelectrode site to CRT. Changes in the timing interval for each leftventricular electrode site are monitored 820.

If a change in the timing interval is detected 830, such as by comparingeach timing interval to a threshold, one or both of the processes shownin FIG. 6 may be performed, sequentially or in parallel. In response toa detected change in the timing interval, an electrode site optimizationprocedure may be performed 835 in a manner discussed above. Assuming adifferent electrode site/vector is selected as one that will provideimproved responsiveness to CRT, the AV delay may be modified 870 and themodified pacing therapy delivered 880 in a manner described herein.Electrode site selection optimization and/or AV delay parameterselection may be performed by the therapy device, by a physician via aprogrammer or APM system, or by any combination of the therapy device,physician, and programmer/APM system.

In response to a detected change in the timing interval, a change in thepatient's hemodynamic status may be diagnosed 840 based on the timinginterval change. An alert signal may be generated 850 and communicatedto a clinician (via a programmer or APM system) in response to thedetected timing interval change. The detected timing interval change maybe used to track progression or regression of the patient's heartfailure status 860. Each of the processes 840, 850, and 860 discussedabove may additionally involve the processes of performing electrodesite optimization 835 and/or AV delay parameter selection, as isindicated in FIG. 6.

FIG. 7 illustrates several electrograms (EGM) and electrocardiograms(ECG) 510-550 for an intrinsic systolic cycle, each measured at adifferent location. For each EGM and ECG 510-550, a voltage measurementis represented on the vertical axis of each plot. Each signal is takenover time, time being represented on the horizontal axis of each plot.

Each portion of an EGM and ECG is typically given an alphabeticdesignation corresponding to a pre-determined period of electricaldepolarization or excitement. For example, the portion of an electrogramthat represents atrial depolarization is commonly referred to as theP-wave (not shown). Similarly, the portion of the electrogram thatrepresents ventricular depolarization is commonly referred to as the QRScomplex comprising a Q-wave, an R-wave, and an S-wave. Moreover, theportion of the electrogram that represents ventricular recovery orrepolarization is commonly referred to as the T-wave (not shown).

The left ventricle EGM 530 illustrates a maximum deflection peakrepresenting the reflexion on the local electrode of the near field(near the electrode) ventricular activation of the left ventriclelabeled LV peak. Also shown in the left ventricle electrogram 530 is thefirst deflection labeled Q1, corresponding to the onset representing thereflexion on the local electrode of the start of the far fieldventricular electrical activation. ECG 540 is a graph for a leadelectrode (e.g., far field electrode), which shows the onset of thefirst deflection of ventricular depolarization that is labeled Q.

FIG. 8 illustrates cardiac signal waveforms 610-650, each representing asignal taken from a different left ventricular electrode site duringintrinsic ventricular depolarization. Each of the waveforms 612-650 isintended to represent a signal received at different electrode sites (orvia different sense vectors) during a single ventricular cycle, or theycould be from different cycles.

Waveform 610 includes two features, a first deflection 612 and a maximumdeflection 613. A time interval 611 is marked between the firstdeflection 612 and the maximum deflection. Waveforms 620-650 aresimilarly marked. As FIG. 8 illustrates, each time interval 611, 621,631, 641 and 651 can be different, even though in some implementationsthey may all be measured from the same ventricle depolarization cycle.The differences in the timing intervals 611, 621, 631, 641 and 651 maybe caused by various abnormalities. As discussed above, in many cases,the effects of CRT on systolic pressure and cardiac output can best berealized by pacing electrode sites with long time intervals. Thus,pacing may be implemented more effectively and/or efficiently by pacingoutput configurations that take into account the relative responsivenessof each electrode site to CRT.

Time interval 631 of waveform 630 is the longest in duration whencompared to the other time intervals 611, 621, 641 and 651 of FIG. 8. Insome embodiments, the electrode site corresponding to waveform 630 maybe the only electrode site of the left ventricle to receive pacingstimulation because it is associated with the longest time interval. Inother embodiments, two or more of the five electrode sites correspondingto waveforms 610-650 may receive pacing stimulation. In such anembodiment, the pacing output configuration, including those electrodesites that receive pacing stimulation and those that do not, may dependon the relative lengths of the timing intervals 611, 621, 631, 641 and651. A comparison between these timing intervals may be made todetermine their relative lengths, as is discussed above.

As was previously discussed, in some implementations, an advancedpatient management or APM system may be employed to remotely monitor apatient's responsiveness to CRT and hemodynamic status. If a change inCRT responsiveness or hemodynamic status is detected, for example theAPM system may signal the implantable device to initiate an evaluationof its pacing output configuration relative to other configurations thatmay include alternative electrode sites and/or pacing parameters. Insome scenarios, selection of the pacing output configuration may beperformed by the implantable device. In other scenarios, the APM systemmay perform the selection, autonomously or with clinician input. Varioustherapeutic and/or diagnostic medical devices coupled to the APM systemcan provide sensing capability for use in detecting the patient'shemodynamic state via a multi-sensor approach. The APM system may becoupled to a variety of patient-external and patient-implantabledevices, each device incorporating a set of sensors which are remotelyaccessible to the APM system.

A user interface may be coupled to the APM allowing a clinician toremotely monitor cardiac functions, as well as other patient conditions.The user interface may be used by the clinician to access informationavailable via the APM. The clinician may also enter information via theuser interface for setting up the pacing output configurationfunctionality. For example, the clinician may select alternate electrodesites or vectors for CRT, particular sensors, hemodynamic statusindicators, indicator levels or sensitivities, and/or electromechanicalparameters. Methods, structures, and/or techniques described herein mayincorporate various APM related methodologies, including featuresdescribed in one or more of the following references: U.S. Pat. Nos.6,221,011; 6,270,457; 6,277,072; 6,280,380; 6,312,378; 6,336,903;6,358,203; 6,368,284; 6,398,728; and 6,440,066, which are herebyincorporated herein by reference.

Adjusting the AV delay in response to selection of a particularelectrode site(s)/vector(s) for optimizing CRT delivery according to thepresent invention may be accomplished in several ways. According to oneapproach, the therapy device may vary the AV delay interval used fordelivering CRT in an atrial tracking or AV sequential pacing mode inaccordance with the sensed or paced atrial rate. Optimal values for theAV delay parameter associated with a particular atrial rate may becomputed as linear functions of an intrinsic conduction measurementtaken when the particular rate is present. Additional details concerningthis approach are described in commonly owned U.S. Pat. No. 7,123,960,which is hereby incorporated herein by reference.

According to another approach, a programmer or APM system may be used toreceive a first data value for use in the execution of one or morealgorithms. One or more suggested therapy device settings are calculatedfrom the one or more algorithms based on the first data value, and theone or more suggested therapy device settings are displayed on aninteractive display screen of the programmer or APM system. In oneembodiment, the first data value is a duration interval of a QRScomplex. From the duration interval, pacing intervals for an AV delayare suggested based on measured P-R intervals, or pacing intervals foran LV offset are suggested based on a measured duration interval of aV-V-interval between a right ventricular event and a left ventricularevent. Additional details concerning this approach are described incommonly owned U.S. Pat. No. 7,181,285, which is hereby incorporatedherein by reference. A further approach is described in commonly ownedU.S. Pat. No. 6,351,673, which is hereby incorporated herein byreference.

Various modifications and additions can be made to the preferredembodiments discussed hereinabove without departing from the scope ofthe present invention. For example, as one of ordinary skill in the artwill understand, various other embodiments are contemplated within thescope of this disclosure, with various other features, intervals,comparisons, and combinations being used to determine the pacing outputconfiguration. Accordingly, the scope of the present invention shouldnot be limited by the particular embodiments described above, but shouldbe defined only by the claims set forth below and equivalents thereof.

1. A method, comprising: sensing, from within a patient, cardiacelectrical signals from a plurality of disparate left ventricularelectrode sites; measuring, for each left ventricular electrode site, atiming interval between first and second cardiac electrical signalfeatures associated with ventricular depolarization, the timing intervalassociated with a degree of responsiveness of the left ventricularelectrode sites to cardiac resynchronization pacing therapy (CRT);detecting a change in the timing interval for each left ventricularelectrode site; and monitoring for a change in hemodynamic status of thepatient based on the detected timing interval change.
 2. The method ofclaim 1, wherein monitoring for the change in the patient's hemodynamicstatus comprises tracking progression or regression of the patient'sheart failure status.
 3. The method of claim 1, further comprisinggenerating an alert signal responsive to the change in the patient'shemodynamic status.
 4. The method of claim 1, further comprisingmodifying selection of one or more of the left ventricular pacing sitesresponsive to the change in the patient's hemodynamic status.
 5. Themethod of claim 1, further comprising modifying one or more pacingdelays responsive to the change in the patient's hemodynamic status. 6.The method of claim 1, further comprising modifying an atrioventricular(AV) delay parameter responsive to the change in the patient'shemodynamic status.
 7. The method of claim 1, further comprisingmodifying delivery of CRT in response to the change in the patient'shemodynamic status.
 8. The method of claim 1, wherein detecting thechange in the timing interval comprises comparing a change in eachtiming interval to a predetermined threshold.
 9. The method of claim 1,wherein detecting the change in the timing interval comprises comparinga change in each timing interval to a threshold based on a Q1-LV timinginterval or a threshold based on a Q-LV timing interval.
 10. The methodof claim 1, wherein detecting the change in the timing intervalcomprises comparing a change in each timing interval to one or morethresholds based on sensed intervals for various cardiac electrode sitesother than Q1-LV and Q-LV timing intervals.
 11. A system, comprising: aplurality of electrodes positionable at a plurality of disparate sitesof the left ventricle and configured for sensing cardiac electricalsignals at the disparate left ventricular sites; a pulse generatorcoupled to the electrodes and configured to deliver at least a cardiacresynchronization therapy (CRT); and a processor coupled to theelectrodes and the pulse generator, the processor configured to measure,for each left ventricular electrode site, a timing interval betweenfirst and second cardiac electrical signal features associated withventricular depolarization, the timing interval associated with a degreeof responsiveness of the left ventricular electrode sites to cardiacresynchronization pacing therapy (CRT), the processor further configuredto detect a change in the timing interval for each left ventricularelectrode site and monitor for a change in hemodynamic status of thepatient based on the detected timing interval change.
 12. The system ofclaim 11, wherein the processor is configured to track progression orregression of the patient's heart failure status.
 13. The system ofclaim 11, wherein the processor is configured to generate an alertsignal responsive to the change in the patient's hemodynamic status. 14.The system of claim 11, wherein the processor is configured to modifyselection of one or more of the left ventricular pacing sites responsiveto the change in the patient's hemodynamic status.
 15. The system ofclaim 11, wherein the processor is configured to modify one or morepacing delays responsive to the change in the patient's hemodynamicstatus.
 16. The system of claim 11, wherein the processor is configuredto modify an atrioventricular (AV) delay parameter responsive to thechange in the patient's hemodynamic status.
 17. The system of claim 11,wherein the processor is configured to modify delivery of CRT inresponse to the change in the patient's hemodynamic status.
 18. Thesystem of claim 11, wherein the processor is configured to compare achange in each timing interval to a predetermined threshold.
 19. Thesystem of claim 11, wherein the processor is configured to compare achange in each timing interval to a threshold based on a Q1-LV timinginterval or a threshold based on a Q-LV timing interval.
 20. The systemof claim 11, wherein the processor is configured to compare a change ineach timing interval to one or more thresholds based on sensed intervalsfor various cardiac electrode sites other than Q1-LV and Q-LV timingintervals.